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Kelley was born in Atlanta, Georgia. Having always wanted to be a doctor yet thwarted by the Great Depression, Kelley instead went into show business starting as a singer with the Lew Forbes Orchestra and in radio. [1]

In 1937 Kelley went to Long Beach, California, to stay with his uncle for two weeks. Those two weeks became a year. Even after returning to Georgia, he decided that California was where he wanted to be. While living in California, Kelley joined a local theater group. There he met Carolyn Dowling, whom he would marry in 1945.

During the Second World War, Kelley served as a bomber crew member. Towards the end of the war, a talent scout for Paramount Pictures saw Kelley in a Navy training film which led to a screen test and a contract, starring in his first motion picture Fear in the Night. Later that same year, Kelley co-starred with such legendary entertainers as Bob Hope and Bing Crosby in the musical comedy Variety Girl. Future TOS guest actor Richard Webb made an appearance as himself in this film.

Kelley went on to co-star with fellow TOS performers Jeff Corey and Whit Bissell as prison escapees in the 1948 thriller Canon City. He appeared in smaller, uncredited roles in several films throughout the 1950s, most notably The Men (1950), House of Bamboo (1955, with Biff Elliot) and The Man in the Gray Flannel Suit (1956, with John Crawford and Kenneth Tobey). He did, however, have a larger, supporting role in the 1955 film noir Illegal, co-starring future Star Trek alumni Robert Ellenstein and Lawrence Dobkin.

Throughout the late 1950s and the 1960s, he starred or appeared primarily in Westerns. He played Morgan Earp in the acclaimed 1957 John Sturges Western Gunfight at the O.K. Corral, in which fellow Trek alumni Whit Bissell and Kenneth Tobey also appeared. Interestingly enough, Kelley had earlier played Ike Clanton on a 1955 episode of You Are There entitled "The Gunfight at the O.K. Corral". He, of course, revisited the O.K. Corral one more time on Star Trek in the 1968 episode, "Spectre of the Gun".

Kelley then appeared in such classic Westerns as Sturges' The Law and Jake Wade (1958), Warlock (1959, with Whit Bissell, Paul Comi, Frank Gorshin, Roy Jenson, and Gary Lockwood) and Town Tamer (1965, with Richard Webb). He also co-starred in a few non-Westerns during this time, including Where Love Has Gone (1964, with Whit Bissell and Anthony Caruso) and the 1965 comedy Marriage on the Rocks, starring crooners Frank Sinatra and Dean Martin.

During this time, he made guest appearances on a number of television series, including Gunsmoke, Perry Mason, Death Valley Days, The Untouchables, and The Fugitive (in an episode with Jason Wingreen). In a 1962 episode of Bonanza, Kelley played a doctor for the first time. That episode also starred another man who would play a Trek doctor, John Hoyt. In 1963, Kelley appeared in an episode of The Virginian with Brian Keith. This episode, entitled "Duel at Shiloh", was edited together with another episode to produce a TV special called The Bull of the West, which aired in 1971. Later in 1963, Kelley guest-starred in a second episode of The Virginian, "Man of Violence", this time with future Star Trek co-star Leonard Nimoy, as well as Trek semi-regular Jim Goodwin. That show marked the second time Kelley played a doctor.

A year later, Kelley made a small appearance in the pilot episode of Roddenberry's series Police Story, which co-starred Steve Ihnat, Malachi Throne, and Grace Lee Whitney. The series was not sold and the pilot was finally aired on television in September, 1967 (when Star Trek's second season was in production). This Police Story, however, is not to be confused with a later NBC series of the same name, on which Kelley guest-starred in 1973.

He appeared in very few movies after being cast as Dr. McCoy; his only non-Trek feature film following the cancellation of Star Trek was the 1972 horror/science fiction B-movie Night of the Lepus, co-starring yet another Trek doctor, Paul Fix, and a group of giant, mutant rabbits. Kelley did, however, continue working in television, guest-starring on shows like Ironside (with Barbara Anderson) and Owen Marshall: Counselor at Law (in an episode with the aforementioned Paul Fix).

A few months prior to making his appearance in "Encounter at Farpoint", Kelley expressed skepticism concerning Star Trek: The Next Generation. "It's a mystery to me why they are doing it," he remarked. "I assume Paramount thinks they can hold onto the Star Trek phenomena. There's no doubt we can't go on forever, so they're trying a way to keep it going. But there's only one Star Trek, and that's ours." (Starlog issue 117, p. 9) A few years later he hosted the short documentary To Boldly Go, a making-of featurette of The Next Generation.

Kelley's only non-Trek role throughout the 1990s (and his final role before his death) was the voice of Viking I in the direct-to-video animated movie The Brave Little Toaster Goes to Mars.

Kelley retired from acting in the mid 1990s, and succumbed to stomach cancer on June 11, 1999, the first of the original Trek cast to pass on, and the only one not to survive into the 21st century. He was survived by Carolyn Dowling, his wife of nearly 54 years, who passed away in October 2004.